The use of mechanical devices ("artificial organs") to replace vital organ function in acute or chronic organ failure has gone from theory to the intensive care bedside in the last 40 years. For 30 of those years our research on artificial organs has been supported by NIH, resulting in devices and techniques now used clinically to treat lung, heart, kidney, and liver failure. One of these techniques (Extracorporeal Life Support, ECMO) can replace lung function for weeks resulting in recovery of otherwise fatal acute lung disease. But ECMO is too complex and invasive to serve as a bridge to lung transplantation. A bridging system is needed because most of the patients listed for lung transplantation die on the waiting list, and because many potential lung donors are not accepted because borderline lung function might prove fatal in the postoperative period without mechanical support. An implantable prosthetic lung which could function for 3-6 months would solve both of these problems, just as the ventricular assist device has been applied to cardiac failure and transplantation. We have applied the expertise of our laboratory to the development of a paracorporeal/implantable total artificial lung; perfused by the right ventricle and capable of total respiratory support. We have demonstrated safety and efficacy of a prototype design during seven days of implantation in sheep. Based on our preliminary studies demonstrating proof of principle, we propose to design and test a total artificial lung to the point of initial clinical trials. In this proposal, we further intend to establish a new collaboration and partnership between medical researchers and bioengineers who have specific expertise in fluid dynamics, gas transport, artificial organ development, extracorporeal support, and pulmonary physiology to develop and refine a TAL such that it can be implanted successfully as a total lung replacement.